The present invention relates to peptides with antigenic or immunogenic determinants, which may be recognized by autoantibodies in the body fluids of patients, who are suffering from systemic lupus erythematosus (SLE).
Diseases of the xe2x80x9crheumatic groupxe2x80x9d are characterized by a large number of clinical phenomena and by a wide spectrum of autoantibodies. The latter are directed against various different components of normal cells. The said diseases include systemic lupus erythematosus (SLE) which may occur spontaneously or may be induced by medicaments. In the case of SLE the occurrence of autoantibodies is particularly frequent, which are directed against components of the cell nucleus (antinuclear antibodies, ANA""s), these including inter alia double strand desoxyribonucleic acid (DS-DNA) and histone proteins, ribonucleic acid (RNA), complexes of DNA and histones as well as enzymes. Histones consist of a number of classes of proteins, the so-called core histones H1A, H2B, H3 and H4, which are found in the nucleosomes, and the linker histones H1 and H5, to which linking functions are attributed in the formation of chromatin. Many attempts have been made to correlate the frequency of autoantibodies, which are directed against special antigens, with certain rheumatic syndromes.
It has been discovered that in the case a patient with SLE autoantibodies against histones (AHA""s, anti-histone autoantibodies) occur more frequently. Normally the xe2x80x9cenzyme linked immuno-sorbent assayxe2x80x9d (ELISA) is utilized for determination, in the case of which the sera of patients and of healthy control subjects are tested on purified cell components (i. e. antigens). Pure histone is inter alia employed as an antigen for the testing of SLE sera.
Furthermore additionally synthetic peptides or those produced by the degradation of natural histones are used, which consist of sequence parts of the said histones.
In this respect it has been seen that in the case of use of the individual histones and histone peptides:
(i) the frequency of a positive reaction in an ELISA is not greater than 50% and that
(ii) the frequency of a positive reaction in the case of patient sera related to other rheumatic diseases is large (false positive results).
Thus recently a study concerning the predictive value of recognition of AHA""s of SLE patients (by means of the LE cell test, Smeenk et al., Scand. J. Rheumatology. Suppl. 56, 78-92, 1985) came to the following conclusion: although 95% of SLE patients were positive in the LE test, in fact the chances that a patient with a positive LE test has SLE are only 27%.
It would therefore be a valuable contribution if the predictive value of diagnostic tests for SLE could be improved, that is to say if the percentage of true-positive results as related to false positive ones could be increased.
It would furthermore be valuable if monoclonal antibodies and antiidiotypical antibodies could be formed, which are specific in the very same manner as the antibodies of SLE patients and if antiidiotypical antibodies (monoclonal antibodies) could be produced, which are directed against these monoclonal antibodies or, respectively, the autoantibodies of SLE patients.
One object of the invention is to a achieve these aims.